http://wiki.jackslab.org/index.php?action=history&feed=atom&title=Ch11_The_Neuronal_Microenvironment 2026-09-11T05:14:23Z 本wiki的该页面的版本历史 MediaWiki 1.19.2 http://wiki.jackslab.org/index.php?title=Ch11_The_Neuronal_Microenvironment&diff=18004&oldid=prev 2024-12-11T10:03:53Z

<p>‎<span dir="auto"><span class="autocomment">少突胶质细胞和雪旺细胞制造并维持髓鞘</span></span></p> <table class='diff diff-contentalign-left'> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr valign='top'> <td colspan='2' style="background-color: white; color:black;">←上一版本</td> <td colspan='2' style="background-color: white; color:black;">2024年12月11日 (三) 10:03的版本</td> </tr><tr><td colspan="2" class="diff-lineno">第411行：</td> <td colspan="2" class="diff-lineno">第411行：</td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 少突胶质细胞和雪旺细胞制造并维持髓鞘 ===</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 少突胶质细胞和雪旺细胞制造并维持髓鞘 ===</div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;Oligodendrocytes and Schwann cells make and sustain myelin&lt;/b&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;Oligodendrocytes and Schwann cells make and sustain myelin&lt;/b&gt;</div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">The primary function of oligodendrocytes as well as of their PNS equivalent, the Schwann cell, is to provide and to maintain myelin sheaths on axons of the central and peripheral nervous systems, respectively. As discussed on p. 199, myelin is the insulating “electrical tape” of the nervous system (see Fig. 7-21B). Oligodendrocytes are present in all areas of the CNS, although their morphological appearance is highly variable and depends on their location within the brain. In regions of the brain that are dominated by myelinated nerve tracts, called white matter, the oligodendrocytes responsible for myelination have a distinctive appearance (Fig. 11-13A). Such an oligodendrocyte has 15 to 30 processes, each of which connects a myelin sheath to the oligodendrocyte’s cell body. Each myelin sheath, which is up to 250 μm wide, wraps many times around the long axis of one axon. The small exposed area of axon between adjacent myelin sheaths is called the node of Ranvier (see pp. 200–201). In gray matter, oligodendrocytes do not produce myelin and exist as perineuronal satellite cells.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">少突胶质细胞及其 PNS 等效物雪旺细胞的主要功能是分别在中枢和周围神经系统的轴突上提供和维持髓鞘。如第 199 页所述，髓鞘是神经系统的绝缘“电胶带”（见图 7-21B）。少突胶质细胞存在于 CNS 的所有区域，尽管它们的形态外观变化很大，并且取决于它们在大脑中的位置。在大脑中以髓鞘神经束（称为白质）为主的区域，负责髓鞘形成的少突胶质细胞具有独特的外观（图 11-13A）。这种少突胶质细胞有 15 到 30 个过程，每个过程将髓鞘连接到少突胶质细胞的细胞体。每个髓鞘宽达 250 μm，围绕一个轴突的长轴缠绕多次。相邻髓鞘之间的轴突小暴露区域称为 Ranvier 节点（见第 200-201 页）。在灰质中，少突胶质细胞不产生髓鞘，以神经元周围卫星细胞的形式存在。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">During the myelination process, the leading edge of one of the processes of the oligodendrocyte cytoplasm wraps around the axon many times (see Fig. 11-13A, upper axon). The cytoplasm is then squeezed out of the many cell layers surrounding the axon in a process called compaction. This process creates layer upon layer of tightly compressed membranes that is called myelin. The myelin sheaths remain continuous with the parent glial cells, which nourish them.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">在髓鞘形成过程中，少突胶质细胞细胞质的一个过程的前缘多次缠绕轴突（参见图 11-13A，上轴突）。然后，细胞质在称为压缩的过程中从轴突周围的许多细胞层中挤出。这个过程会产生一层又一层的紧密压缩膜，称为髓鞘。髓鞘与母本神经胶质细胞保持连续，从而滋养它们。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">In the PNS, a single Schwann cell provides a single myelin segment to a single axon of a myelinated nerve (see Fig. 11-13B). This situation stands in contrast to that in the CNS, where one oligodendrocyte myelinates many axons. The process of myelination that occurs in the PNS is analogous to that outlined for oligodendrocytes. Axons of unmyelinated nerves are also associated with Schwann cells. In this case, the axons indent the surface of the Schwann cell and are completely surrounded by Schwann cell cytoplasm (Fig. 11-14).</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">在 PNS 中，单个雪旺细胞为有髓神经的单个轴突提供单个髓鞘段（见图 11-13B）。这种情况与 CNS 的情况形成鲜明对比，在 CNS 中，一个少突胶质细胞髓鞘化许多轴突。PNS 中发生的髓鞘形成过程类似于少突胶质细胞概述的过程。无髓神经的轴突也与雪旺细胞有关。在这种情况下，轴突压入雪旺细胞表面，并完全被雪旺细胞细胞质包围（图 11-14）。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Myelin has a biochemical composition different from that of the oligodendrocyte or Schwann cell plasma membrane from which it arose. Although PNS myelin and CNS myelin look similar, some of the constituent proteins are different (Table 11-4). For example, proteolipid protein is the most common protein in CNS myelin (~50% of total protein) but is absent in PNS myelin. Conversely, P0 is found almost exclusively in PNS myelin.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">髓鞘的生化成分不同于它产生的少突胶质细胞或雪旺细胞质膜的生化成分。尽管 PNS 髓鞘和 CNS 髓鞘看起来相似，但一些组成蛋白是不同的（表 11-4）。例如，蛋白脂蛋白是 CNS 髓鞘中最常见的蛋白质（占总蛋白的 ~50%），但在 PNS 髓鞘中不存在。相反，P0 几乎只存在于 PNS 髓鞘中。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Myelination greatly enhances conduction of the action potential down the axon because it allows the regenerative electrical event to skip from one node to the next rather than gradually spreading down the whole extent of the axon. This process is called saltatory conduction (see pp. 200–201). Besides being responsible for CNS myelin, oligodendrocytes play another key role in saltatory conduction: they induce the clustering of Na+ channels at the nodes (see Fig. 12-5C), which is essential for saltatory conduction.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">髓鞘形成极大地增强了动作电位沿轴突的传导，因为它允许再生电事件从一个节点跳到另一个节点，而不是逐渐沿着轴突的整个范围扩散。这个过程称为盐传导（见第 200-201 页）。除了负责 CNS 髓鞘外，少突胶质细胞在盐性传导中还起着另一个关键作用：它们诱导 Na+ 通道在节点处聚集（见图 12-5C），这对于盐性传导至关重要。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">It is well known that severed axons in the PNS can regenerate with restoration of lost function. Regrowth of these damaged axons is coordinated by the Schwann cells in the distal portion of the cut nerve. Severed axons in the CNS do not show functional regrowth, in part because of the growth-retarding nature of myelin-associated glycoproteins (see pp. 267–268).</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">众所周知，PNS 中被切断的轴突可以通过恢复失去的功能而再生。这些受损轴突的再生由切割神经远端的雪旺细胞协调。CNS 中切断的轴突不显示功能性再生，部分原因是髓鞘相关糖蛋白的生长延缓性质（参见第 267-268 页）。</ins></div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td></tr> </table>

Comcat http://wiki.jackslab.org/index.php?title=Ch11_The_Neuronal_Microenvironment&diff=18003&oldid=prev 2024-12-11T10:00:44Z

<p>‎<span dir="auto"><span class="autocomment">星形胶质细胞合成神经递质，从细胞外间隙吸收它们，并具有神经递质受体</span></span></p> <table class='diff diff-contentalign-left'> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr valign='top'> <td colspan='2' style="background-color: white; color:black;">←上一版本</td> <td colspan='2' style="background-color: white; color:black;">2024年12月11日 (三) 10:00的版本</td> </tr><tr><td colspan="2" class="diff-lineno">第351行：</td> <td colspan="2" class="diff-lineno">第351行：</td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 星形胶质细胞合成神经递质，从细胞外间隙吸收它们，并具有神经递质受体 ===</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 星形胶质细胞合成神经递质，从细胞外间隙吸收它们，并具有神经递质受体 ===</div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;Astrocytes synthesize neurotransmitters, take them up from the extracellular space, and have neurotransmitter receptors&lt;/b&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;Astrocytes synthesize neurotransmitters, take them up from the extracellular space, and have neurotransmitter receptors&lt;/b&gt;</div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Astrocytes synthesize at least 20 neuroactive compounds, including both glutamate and gamma-aminobutyric acid (GABA). Neurons can manufacture glutamate from glucose or from the immediate precursor molecule glutamine (Fig. 11-12). The glutamine pathway appears to be the primary one in the synthesis of synaptically released glutamate. Glutamine, however, is manufactured only in astrocytes by use of the astrocyte-specific enzyme glutamine synthetase to convert glutamate to glutamine. Astrocytes release this glutamine into the BECF through the SNAT3 and SNAT5 transporters (SLC38 family, see Table 5-4) for uptake by neurons through SNAT1 and SNAT2. Consistent with its role in the synthesis of glutamate for neurotransmission, glutamine synthetase is localized to astrocytic processes surrounding glutamatergic synapses. In the presynaptic ter- minals of neurons, glutaminase converts the glutamine to glutamate for release into the synaptic cleft by the presynaptic terminal. Finally, astrocytes take up much of the synaptically released glutamate to complete this glutamateglutamine cycle. Disruption of this metabolic interaction between astrocytes and neurons can depress glutamatedependent synaptic transmission.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">星形胶质细胞合成至少 20 种神经活性化合物，包括谷氨酸和 γ-氨基丁酸 （GABA）。神经元可以从葡萄糖或直接前体分子谷氨酰胺中制造谷氨酸（图 11-12）。谷氨酰胺途径似乎是合成突触释放的谷氨酸的主要途径。然而，谷氨酰胺仅在星形胶质细胞中通过使用星形胶质细胞特异性酶谷氨酰胺合成酶将谷氨酸转化为谷氨酰胺而制造。星形胶质细胞通过 SNAT3 和 SNAT5 转运蛋白（SLC38 家族，见表 5-4）将这种谷氨酰胺释放到 BECF 中，以便神经元通过 SNAT1 和 SNAT2 摄取。与其在谷氨酸合成神经传递中的作用一致，谷氨酰胺合成酶定位于谷氨酸能突触周围的星形胶质细胞过程。在神经元的突触前末端，谷氨酰胺酶将谷氨酰胺转化为谷氨酸，由突触前末端释放到突触间隙中。最后，星形胶质细胞吸收大部分突触释放的谷氨酸以完成这个谷氨酸谷氨酰胺循环。星形胶质细胞和神经元之间这种代谢相互作用的破坏会抑制谷氨酸依赖性突触传递。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Glutamine derived from astrocytes is also important for synthesis of the brain’s most prevalent inhibitory neurotransmitter, GABA. In the neuron, the enzyme glutamic acid decarboxylase converts glutamate (generated from glutamine) to GABA (see Fig. 13-8A). Because astrocytes play such an important role in the synthesis of synaptic transmitters, these glial cells are in a position to modulate synaptic efficacy.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">源自星形胶质细胞的谷氨酰胺对于合成大脑最普遍的抑制性神经递质 GABA 也很重要。在神经元中，谷氨酸脱羧酶将谷氨酸（由谷氨酰胺产生）转化为 GABA（见图 13-8A）。由于星形胶质细胞在突触递质的合成中起着如此重要的作用，因此这些神经胶质细胞能够调节突触功效。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Astrocytes have high-affinity uptake systems for the excitatory transmitter glutamate and the inhibitory transmitter GABA. In the case of glutamate uptake, mediated by EAAT1 and EAAT2 (SLC1 family, see Table 5-4), astrocytes appear to play the dominant role compared with neurons or other glial cells. Glutamate moves into cells accompanied by two Na+ ions and an H+ ion, with one K+ ion moving in the opposite direction (see Fig. 11-12). Because a net positive charge moves into the cell, glutamate uptake causes membrane depolarization. The presynaptic cytoplasm may contain glutamate at a concentration as high as 10 mM, and vesicles may contain as much as 100 mM glutamate. Nevertheless, the glutamate uptake systems can maintain extracellular glutamate at concentrations as low as ~1 μM, which is crucial for normal brain function.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">星形胶质细胞具有兴奋性递质谷氨酸和抑制性递质 GABA 的高亲和力摄取系统。在由 EAAT1 和 EAAT2 （SLC1 家族，见表 5-4） 介导的谷氨酸摄取的情况下，与神经元或其他神经胶质细胞相比，星形胶质细胞似乎起主导作用。谷氨酸在两个 Na+ 离子和一个 H+ 离子的陪伴下进入细胞，其中一个 K+ 离子沿相反方向移动（见图 11-12）。因为净正电荷进入细胞，谷氨酸摄取导致膜去极化。突触前细胞质可能含有浓度高达 10 mM 的谷氨酸，囊泡可能含有高达 100 mM 的谷氨酸。然而，谷氨酸摄取系统可以将细胞外谷氨酸维持在低至 ~1 μM 的浓度，这对正常的大脑功能至关重要。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Neurotransmitter uptake systems are important because they help terminate the action of synaptically released neurotransmitters. Astrocyte processes frequently surround synaptic junctions and are ideally placed for this function. Under pathological conditions in which transmembrane ion gradients break down, high-affinity uptake systems may work in reverse and release transmitters, such as glutamate, into the BECF (Box 11-4).</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">神经递质摄取系统很重要，因为它们有助于终止突触释放的神经递质的作用。星形胶质细胞突起经常围绕突触连接，是实现此功能的理想位置。在跨膜离子梯度分解的病理条件下，高亲和力摄取系统可以反向工作并将谷氨酸等递质释放到 BECF 中（框 11-4）。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Astrocytes express a wide variety of ionotropic and metabotropic neurotransmitter receptors that are similar or identical to those present on neuronal membranes. As in neurons, activation of these receptors can open ion channels or generate second messengers. In most astrocytes, glutamate produces depolarization by increasing Na+ permeability, whereas GABA hyperpolarizes cells by opening Cl− channels, similar to the situation in neurons (see pp. 326–327). Transmitter substances released by neurons at synapses can diffuse in the BECF to activate nearby receptors on astrocytes, thus providing, at least theoretically, a form of neuronal-glial signaling.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">星形胶质细胞表达多种离子型和代谢型神经递质受体，这些受体与神经元膜上的受体相似或相同。与神经元一样，这些受体的激活可以打开离子通道或产生第二信使。在大多数星形胶质细胞中，谷氨酸通过增加 Na+ 通透性产生去极化，而 GABA 通过打开 Cl− 通道使细胞超极化，类似于神经元中的情况（参见第 326-327 页）。神经元在突触处释放的递质物质可以在 BECF 中扩散以激活星形胶质细胞上的附近受体，从而至少在理论上提供一种神经元-神经胶质细胞信号传导形式。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Astrocytes apparently can actively enhance or depress neuronal discharge and synaptic transmission by releasing neurotransmitters that they have taken up or synthesized. The release mechanisms are diverse and include stimulation by certain neurotransmitters, a fall in [Ca2+]o, or depolarization by elevated [K+]o. Applying glutamate to cultured astrocytes increases [Ca2+]i, which may oscillate. Moreover, these increases in [Ca2+]i can travel in waves from astrocyte to astrocyte through gap junctions or through a propagated front of extracellular ATP release that activates astrocytic purinergic receptors, thereby increasing [Ca2+]i and releasing more ATP. These [Ca2+]i waves—perhaps by triggering the release of a neurotransmitter from the astrocyte—can lead to changes in the activity of nearby neurons. This interaction represents another form of glial-neuronal communication.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">星形胶质细胞显然可以通过释放它们已经吸收或合成的神经递质来主动增强或抑制神经元放电和突触传递。释放机制多种多样，包括某些神经递质的刺激、[Ca2+]o 的下降或 [K+]o 升高的去极化。将谷氨酸应用于培养的星形胶质细胞会增加 [Ca2+]i，这可能会振荡。此外，这些 [Ca2+]i 的增加可以通过间隙连接或通过激活星形胶质细胞嘌呤能受体的细胞外 ATP 释放的传播前沿，从而增加 [Ca2+]i 并释放更多的 ATP。这些 [Ca2+]i 波（可能是通过触发星形胶质细胞释放神经递质）可导致附近神经元活动的变化。这种相互作用代表了另一种形式的神经胶质-神经元通讯。</ins></div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td></tr> </table>

Comcat http://wiki.jackslab.org/index.php?title=Ch11_The_Neuronal_Microenvironment&diff=18002&oldid=prev 2024-12-11T09:56:59Z

<p>‎<span dir="auto"><span class="autocomment">间隙连接将星形胶质细胞彼此偶联，允许小溶质扩散</span></span></p> <table class='diff diff-contentalign-left'> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr valign='top'> <td colspan='2' style="background-color: white; color:black;">←上一版本</td> <td colspan='2' style="background-color: white; color:black;">2024年12月11日 (三) 09:56的版本</td> </tr><tr><td colspan="2" class="diff-lineno">第332行：</td> <td colspan="2" class="diff-lineno">第332行：</td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 间隙连接将星形胶质细胞彼此偶联，允许小溶质扩散 ===</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 间隙连接将星形胶质细胞彼此偶联，允许小溶质扩散 ===</div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;Gap junctions couple astrocytes to one another, allowing diffusion of small solutes&lt;/b&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;Gap junctions couple astrocytes to one another, allowing diffusion of small solutes&lt;/b&gt;</div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">The anatomical substrate for cell-cell coupling among astrocytes is the gap junction, which is composed of membrane proteins called connexins that form large aqueous pores connecting the cytoplasm of two adjacent cells (see pp. 158– 159). Coupling between astrocytes is strong because hundreds of gap junction channels may be present between two astrocytes. Astrocytes may also be weakly coupled to oligodendrocytes. Ions and organic molecules that are up to 1 kDa in size, regardless of charge, can diffuse from one cell into another through these large channels. Thus, a broad range of biologically important molecules, including nucleotides, sugars, amino acids, small peptides, cAMP, Ca2+, and inositol 1,4,5-trisphosphate (IP3), have access to this pathway.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">星形胶质细胞之间细胞-细胞偶联的解剖基质是间隙连接，它由称为连接蛋白的膜蛋白组成，这些膜蛋白形成连接两个相邻细胞的细胞质的大水孔（参见第 158-159 页）。星形胶质细胞之间的偶联性很强，因为两个星形胶质细胞之间可能存在数百个间隙连接通道。星形胶质细胞也可能与少突胶质细胞弱偶联。大小高达 1 kDa 的离子和有机分子，无论电荷如何，都可以通过这些大通道从一个细胞扩散到另一个细胞。因此，广泛的生物学重要分子，包括核苷酸、糖、氨基酸、小肽、cAMP、Ca2+ 和肌醇 1,4,5-三磷酸 （IP3），都可以进入该途径。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Gap junctions may coordinate the metabolic and electrical activities of cell populations, amplify the consequences of signal transduction, and control intrinsic proliferative capacity. The strong coupling among astrocytes ensures that all cells in the aggregate have similar intracellular concentrations of ions and small molecules and similar membrane potentials. Thus, the network of astrocytes functionally behaves like a syncytium, much like the myocytes in the heart (see p. 483). In ways that are not yet clear, gap junctional communication can be important for the control of cellular proliferation. The most common brain cell–derived tumors in the CNS arise from astrocytes. Malignant astrocyte tumors, like malignant neoplasms derived from other cells that are normally coupled (e.g., liver cells), lack gap junctions. N11-5</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">间隙连接可以协调细胞群的代谢和电活动，放大信号转导的后果，并控制内在的增殖能力。星形胶质细胞之间的强偶联确保聚集体中的所有细胞都具有相似的细胞内离子和小分子浓度以及相似的膜电位。因此，星形胶质细胞网络在功能上表现得像合胞体，很像心脏中的肌细胞（见第 483 页）。以尚不清楚的方式，间隙连接通信对于控制细胞增殖可能很重要。CNS 中最常见的脑细胞来源肿瘤起源于星形胶质细胞。恶性星形胶质细胞肿瘤，如源自正常偶联的其他细胞（例如肝细胞）的恶性肿瘤，缺乏间隙连接。编号 N11-5</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">The coupling among astrocytes may also play an important role in controlling [K+]o by a mechanism known as spatial buffering. The selective K+ permeability of glia, together with their low-resistance cell-cell connections, permits them to transport K+ from focal areas of high [K+]o, where a portion of the glial syncytium would be depolarized, to areas of normal [K+]o, where the glial syncytium would be more normally polarized (see Fig. 11-11B). Redistribution of K+ proceeds by way of a current loop in which K+ enters glial cells at the point of high [K+]o and leaves them at sites of normal [K+]o, with the extracellular flow of Na+ completing this circuit. At a site of high neuronal activity, [K+]o might rise to 12 mM, which would produce a very large depolarization of an isolated, uncoupled astrocyte. However, because of the electrical coupling among astrocytes, the Vm of the affected astrocyte remains more negative than the equilibrium potential for K+ (EK) predicted for a [K+]o of 12 mM. Thus, K+ would tend to passively enter coupled astrocytes through channels at sites of high [K+]o. N11-6 As discussed in the preceding section, K+ may also enter the astrocyte by transporters.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">星形胶质细胞之间的偶联也可能通过一种称为空间缓冲的机制在控制 [K+]o 中发挥重要作用。神经胶质细胞的选择性 K+ 通透性，以及它们的低电阻细胞间连接，使它们能够将 K+ 从高 [K+]o 的局灶区域（其中一部分神经胶质合胞体会去极化）转运到正常 [K+]o 的区域，在那里神经胶质细胞合胞体会更正常地极化（见图 11-11B）。K+ 的重新分布通过电流回路进行，其中 K+ 在高 [K+]o 点进入神经胶质细胞，并将它们留在正常 [K+]o 的位点，Na+ 的细胞外流动完成该回路。在神经元活性高的位点，[K+]o 可能会上升到 12 mM，这将产生分离的、未偶联的星形胶质细胞的非常大的去极化。然而，由于星形胶质细胞之间的电耦合，受影响的星形胶质细胞的 Vm 仍然比预测的 [K+]o 为 12 mM 的 K+ （EK） 的平衡电位更负。因此，K+ 倾向于通过高 [K+]o 位点的通道被动进入偶联的星形胶质细胞。N11-6 如上一节所述，K+ 也可能通过转运蛋白进入星形胶质细胞。</ins></div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td></tr> </table>

Comcat http://wiki.jackslab.org/index.php?title=Ch11_The_Neuronal_Microenvironment&diff=18001&oldid=prev 2024-12-11T09:55:23Z

<p>‎<span dir="auto"><span class="autocomment">星形胶质细胞主要可渗透 K+，也有助于调节 [K+]o</span></span></p> <table class='diff diff-contentalign-left'> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr valign='top'> <td colspan='2' style="background-color: white; color:black;">←上一版本</td> <td colspan='2' style="background-color: white; color:black;">2024年12月11日 (三) 09:55的版本</td> </tr><tr><td colspan="2" class="diff-lineno">第313行：</td> <td colspan="2" class="diff-lineno">第313行：</td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 星形胶质细胞主要可渗透 K+，也有助于调节 [K+]o ===</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 星形胶质细胞主要可渗透 K+，也有助于调节 [K+]o ===</div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;Astrocytes are predominantly permeable to K+ and also help regulate [K+]o&lt;/b&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;Astrocytes are predominantly permeable to K+ and also help regulate [K+]o&lt;/b&gt;</div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">The membrane potential of glial cells is more negative than that of neurons. For example, astrocytes have a Vm of about −85 mV, whereas the resting neuronal Vm is about −65 mV. Because the equilibrium potential for K+ is about −90 mV in both neurons and glia, the more negative Vm in astrocytes indicates that glial membranes have higher K+ selectivity than neuronal membranes do (see p. 148). Although glial cells express a variety of K+ channels, inwardly rectifying K+ channels seem to be important in setting the resting potential. These channels are voltage gated and are open at membrane potentials that are more negative than about −80 mV, close to the observed resting potential of astrocytes. Astrocytes express many other voltage-gated ion channels that were once thought to be restricted to neurons. The significance of voltage-gated Na+ and Ca2+ channels in glial cells is unknown. Because the ratio of Na+ to K+ channels is low in adult astrocytes, these cells are not capable of regenerative electrical responses such as the action potential.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">神经胶质细胞的膜电位比神经元的膜电位更负。例如，星形胶质细胞的 Vm 约为 -85 mV，而静息神经元的 Vm 约为 -65 mV。因为 K+ 的平衡电位在神经元和神经胶质细胞中约为 -90 mV，所以星形胶质细胞中更多的负 Vm 表明神经胶质细胞膜具有比神经元膜更高的 K+ 选择性（见第 148 页）。尽管神经胶质细胞表达多种 K+ 通道，但向内整流 K+ 通道似乎在设置静息电位方面很重要。这些通道是电压门控的，并且在比约 -80 mV 更负的膜电位处开放，接近观察到的星形胶质细胞的静息电位。星形胶质细胞表达许多其他电压门控离子通道，这些离子通道曾经被认为仅限于神经元。电压门控 Na + 和 Ca2 + 通道在神经胶质细胞中的意义尚不清楚。由于成年星形胶质细胞中 Na + 与 K + 通道的比率较低，因此这些细胞无法产生再生电反应，例如动作电位。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">One consequence of the higher K+ selectivity of astrocytes is that the Vm of astrocytes is far more sensitive than that of neurons to changes in [K+]o. For example, when [K+]o is raised from 4 to 20 mM, astrocytes depolarize by ~25 mV versus only ~5 mV for neurons. This relative insensitivity of neuronal resting potential to changes in [K+]o in the “physiological” range may have emerged as an adaptive feature that stabilizes the resting potential of neurons in the face of the transient increases in [K+]o that accompany neuronal activity. In contrast, natural stimulation, such as viewing visual targets of different shapes or orientations, can cause depolarizations of up to 10 mV in astrocytes of the visual cortex. The accumulation of extracellular K+ that is secondary to neural activity may serve as a signal—to glial cells—that is proportional to the extent of the activity. For example, small increases in [K+]o cause astrocytes to increase their glucose metabolism and to provide more lactate for active neurons. In addition, the depolarization that is triggered by the increased [K+]o leads to the influx of HCO3− into astrocytes by the electrogenic Na/HCO3 cotransporter (see p. 122); this influx of bicarbonate in turn causes a fall in extracellular pH that may diminish neuronal excitability. N11-4</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">星形胶质细胞较高的 K+ 选择性的一个结果是，星形胶质细胞的 Vm 比神经元对 [K+]o 的变化更敏感。例如，当 [K+]o 从 4 mM 升高到 20 mM 时，星形胶质细胞去极化 ~25 mV，而神经元的去极化仅为 ~5 mV。神经元静息电位对“生理”范围内 [K+]o 变化的这种相对不敏感可能已成为一种适应性特征，当神经元活动伴随 [K+]o 的瞬时增加时，它可以稳定神经元的静息电位。相比之下，自然刺激，例如观察不同形状或方向的视觉目标，可导致视觉皮层星形胶质细胞出现高达 10 mV 的去极化。继发于神经活动的细胞外 K+ 积累可能作为神经胶质细胞的信号，该信号与活动程度成正比。例如，[K+]o 的小幅增加会导致星形胶质细胞增加其葡萄糖代谢并为活跃的神经元提供更多的乳酸。此外，由增加的 [K+]o 触发的去极化导致 HCO3− 通过电原 Na/HCO3 协同转运蛋白流入星形胶质细胞（见第 122 页）;碳酸氢盐的流入反过来会导致细胞外 pH 值下降，这可能会降低神经元的兴奋性。编号 N11-4</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Not only do astrocytes respond to changes in [K+]o, they also help regulate it (Fig. 11-11A). The need for homeostatic control of [K+]o is clear because changes in brain [K+]o can influence transmitter release, cerebral blood flow, cell volume, glucose metabolism, and neuronal activity. Active neurons lose K+ into the BECF, and the resulting increased [K+]o tends to act as a positive-feedback signal that increases excitability by further depolarizing neurons. This potentially unstable situation is opposed by efficient mechanisms that expedite K+ removal and limit its accumulation to a maximum level of 10 to 12 mM, the so-called ceiling level. [K+]o would rise far above this ceiling with intense neural activity if K+ clearance depended solely on passive redistribution of K+ in the BECF. Neurons and blood vessels can contribute to K+ homeostasis, but glial mechanisms are probably most important. Astrocytes can take up K+ in response to elevated [K+]o by three major mechanisms: the Na-K pump, the Na/K/Cl cotransporter, and the uptake of K+ and Cl− through channels. Conversely, when neural activity decreases, K+ and Cl− leave the astrocytes through ion channels.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">星形胶质细胞不仅对 [K+]o 的变化做出反应，还有助于调节它（图 11-11A）。对 [K+]o 进行稳态控制的需求是显而易见的，因为大脑 [K+]o 的变化会影响递质释放、脑血流量、细胞体积、葡萄糖代谢和神经元活动。活跃的神经元将 K+ 丢失到 BECF 中，由此产生的 [K+]o 增加往往充当正反馈信号，通过进一步去极化神经元来增加兴奋性。这种潜在的不稳定情况与加速 K+ 去除并将其积累限制在 10 至 12 mM 的最大水平（即所谓的上限水平）的有效机制相反。如果 K+ 清除仅取决于 BECF 中 K+ 的被动重新分配，则 [K+]o 将远远超过这个上限。神经元和血管可促进 K+ 稳态，但神经胶质机制可能是最重要的。星形胶质细胞可以通过三种主要机制响应 [K+]o 升高而摄取 K+：Na-K 泵、Na/K/Cl 协同转运蛋白以及通过通道摄取 K+ 和 Cl−。相反，当神经活动降低时，K+ 和 Cl− 通过离子通道离开星形胶质细胞。</ins></div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td></tr> </table>

Comcat http://wiki.jackslab.org/index.php?title=Ch11_The_Neuronal_Microenvironment&diff=18000&oldid=prev 2024-12-11T09:52:47Z

<p>‎<span dir="auto"><span class="autocomment">星形胶质细胞以乳酸的形式为神经元提供燃料</span></span></p> <table class='diff diff-contentalign-left'> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr valign='top'> <td colspan='2' style="background-color: white; color:black;">←上一版本</td> <td colspan='2' style="background-color: white; color:black;">2024年12月11日 (三) 09:52的版本</td> </tr><tr><td colspan="2" class="diff-lineno">第289行：</td> <td colspan="2" class="diff-lineno">第289行：</td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 星形胶质细胞以乳酸的形式为神经元提供燃料 ===</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 星形胶质细胞以乳酸的形式为神经元提供燃料 ===</div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;Astrocytes supply fuel to neurons in the form of lactic acid&lt;/b&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;Astrocytes supply fuel to neurons in the form of lactic acid&lt;/b&gt;</div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Astrocytes have great numbers of extremely elaborate processes that closely approach both blood vessels and neurons. This arrangement led to the idea that astrocytes transport substances between the blood and neurons. This notion may be true, but it has not been proved. Throughout the brain, astrocytes envelop neurons, and both cells bathe in a common BECF. Therefore, astrocytes are ideally positioned to modify and to control the immediate environment of neurons. Most astrocytes in the brain are traditionally subdivided into fibrous and protoplasmic types (see Table 11-3). Fibrous astrocytes (found mainly in white matter) have long, thin, and well-defined processes, whereas protoplasmic astrocytes (found mainly in gray matter) have shorter, frilly processes (see Fig. 11-9). Astrocytes are evenly spaced. In cortical regions, the dense processes of an individual astrocyte define its spatial domain, into which adjacent astrocytes do not encroach. The cytoskeleton of these and other types of astrocytes contains an identifying intermediate filament (see p. 23) that is composed of a unique protein called glial fibrillar acidic protein (GFAP). The basic physiological properties of both types of astrocyte are similar, but specialized features, such as the expression of neurotransmitter receptors, vary among astrocytes from different brain regions.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">星形胶质细胞具有大量极其复杂的过程，它们紧密接近血管和神经元。这种安排导致了星形胶质细胞在血液和神经元之间运输物质的想法。这个概念可能是正确的，但尚未得到证实。在整个大脑中，星形胶质细胞包裹着神经元，两个细胞都沐浴在共同的 BECF 中。因此，星形胶质细胞非常适合修饰和控制神经元的直接环境。大脑中的大多数星形胶质细胞传统上分为纤维型和原生质型（见表 11-3）。纤维星形胶质细胞（主要存在于白质中）具有长而薄且界限分明的突起，而原生质星形胶质细胞（主要存在于灰质中）具有较短的褶边突起（见图 11-9）。星形胶质细胞分布均匀。在皮质区域，单个星形胶质细胞的致密突定义了它的空间域，相邻的星形胶质细胞不会侵入该空间域。这些和其他类型的星形胶质细胞的细胞骨架包含一个识别中间丝（见第 23 页），它由一种称为神经胶质纤维酸性蛋白 （GFAP） 的独特蛋白质组成。两种星形胶质细胞的基本生理特性相似，但来自不同大脑区域的星形胶质细胞的特殊特征（例如神经递质受体的表达）各不相同。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">During development, another type of astrocyte called the radial glial cell (see pp. 263–265) is also present. As discussed on p. 267, these cells create an organized “scaffolding” by spanning the developing forebrain from the ventricle to the pial surface. Astrocytes in the retina and cerebellum are similar in appearance to radial glial cells. Like astrocytes elsewhere, these cells contain the intermediate filament GFAP. Retinal astrocytes, called Müller cells, are oriented so that they span the entire width of the retina. Bergmann glial cells in the cerebellum have processes that run parallel to the processes of Purkinje cells.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">在发育过程中，还存在另一种称为放射状胶质细胞的星形胶质细胞（参见第 263-265 页）。如第 267 页所述，这些细胞通过将发育中的前脑从心室跨越到软脑膜表面来创建一个有组织的“支架”。视网膜和小脑中的星形胶质细胞在外观上与放射状神经胶质细胞相似。与其他地方的星形胶质细胞一样，这些细胞包含中间丝 GFAP。视网膜星形胶质细胞，称为 Müller 细胞，其定向使其跨越视网膜的整个宽度。小脑中的 Bergmann 神经胶质细胞具有与浦肯野细胞平行的过程。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Astrocytes store virtually all the glycogen present in the adult brain. They also contain all the enzymes needed for metabolizing glycogen. The brain’s high metabolic needs are primarily met by glucose transferred from blood because the brain’s glucose supply in the form of glycogen is very limited. In the absence of glucose from blood, astrocytic glycogen could sustain the brain for only 5 to 10 minutes. As implied, astrocytes can share with neurons the energy stored in glycogen, but not by the direct release of glucose into the BECF. Instead, astrocytes break glycogen down to glucose and even further to lactate, which is transferred to nearby neurons where it can be aerobically metabolized (Fig. 11-10). The extent to which this metabolic interaction takes place under normal conditions is not known, but it may be important during periods of intense neuronal activity, when the demand for glucose exceeds the supply from blood.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">星形胶质细胞几乎储存了成人大脑中存在的所有糖原。它们还包含代谢糖原所需的所有酶。大脑的高代谢需求主要由从血液中转移的葡萄糖来满足，因为大脑以糖原形式提供的葡萄糖供应非常有限。在血液中没有葡萄糖的情况下，星形胶质细胞糖原只能维持大脑 5 到 10 分钟。正如暗示的那样，星形胶质细胞可以与神经元共享储存在糖原中的能量，但不能通过将葡萄糖直接释放到 BECF 中。相反，星形胶质细胞将糖原分解成葡萄糖，甚至进一步分解成乳酸，乳酸被转移到附近的神经元，在那里可以进行有氧代谢（图 11-10）。这种代谢相互作用在正常情况下发生的程度尚不清楚，但在神经元活动激烈期间可能很重要，此时对葡萄糖的需求超过血液的供应。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Astrocytes can also provide fuel to neurons in the form of lactate derived directly from glucose, independent of glycogen. Glucose entering the brain from blood first encounters the astrocytic endfoot. Although it can diffuse past this point to neurons, glucose may be preferentially taken up by astrocytes and shuttled through astrocytic glycolysis to lactic acid, a significant portion of which is excreted into the BECF surrounding neurons. Several observations support the notion that astrocytes provide lactate to neurons. First, astrocytes have higher anaerobic metabolic rates and export much more lactate than do neurons. Second, neurons and their axons function normally when glucose is replaced by lactate, and some neurons seem to prefer lactate to glucose as fuel. Note that when they are aerobically metabolized, the two molecules of lactate derived from the breakdown of one molecule of glucose provide nearly as much ATP (28 molecules) as the complete oxidation of glucose itself (30 molecules of ATP; see Table 58-4). The advantage of this scheme for neuronal function is that it provides a form of substrate buffering, a second energy reservoir that is available to neurons. The availability of glucose in the neuronal microenvironment depends on moment-to-moment supply from the blood and varies as a result of changes in neural activity. The concentration of extracellular lactate, however, is buffered against such variability by the surrounding astrocytes, which continuously shuttle lactate to the BECF by metabolizing glucose or by breaking down glycogen.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">星形胶质细胞还可以以直接来自葡萄糖的乳酸形式为神经元提供燃料，与糖原无关。葡萄糖从血液进入大脑首先遇到星形胶质细胞型末端足。尽管葡萄糖可以扩散到神经元，但葡萄糖可能优先被星形胶质细胞吸收并通过星形胶质细胞糖酵解转化为乳酸，其中很大一部分排泄到神经元周围的 BECF 中。一些观察结果支持星形胶质细胞为神经元提供乳酸的观点。首先，星形胶质细胞具有更高的厌氧代谢率，并且比神经元输出更多的乳酸。其次，当葡萄糖被乳酸取代时，神经元及其轴突功能正常，一些神经元似乎更喜欢乳酸而不是葡萄糖作为燃料。请注意，当它们被有氧代谢时，由一个葡萄糖分子分解产生的两个乳酸分子提供的 ATP（28 个分子）几乎与葡萄糖本身的完全氧化（30 个 ATP 分子;见表 58-4）一样多。这种神经元功能方案的优势在于它提供了一种底物缓冲形式，即神经元可用的第二个能量库。神经元微环境中葡萄糖的可用性取决于血液的即时供应，并因神经活动的变化而变化。然而，细胞外乳酸的浓度被周围的星形胶质细胞缓冲到这种变化，星形胶质细胞通过代谢葡萄糖或分解糖原不断将乳酸穿梭到 BECF。</ins></div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td></tr> </table>

Comcat http://wiki.jackslab.org/index.php?title=Ch11_The_Neuronal_Microenvironment&diff=17999&oldid=prev 2024-12-11T09:50:00Z

<p>‎<span dir="auto"><span class="autocomment">神经胶质细胞占大脑体积的一半，数量超过神经元</span></span></p> <table class='diff diff-contentalign-left'> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr valign='top'> <td colspan='2' style="background-color: white; color:black;">←上一版本</td> <td colspan='2' style="background-color: white; color:black;">2024年12月11日 (三) 09:50的版本</td> </tr><tr><td colspan="2" class="diff-lineno">第275行：</td> <td colspan="2" class="diff-lineno">第275行：</td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 神经胶质细胞占大脑体积的一半，数量超过神经元 ===</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 神经胶质细胞占大脑体积的一半，数量超过神经元 ===</div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;Glial cells constitute half the volume of the brain and outnumber neurons&lt;/b&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;Glial cells constitute half the volume of the brain and outnumber neurons&lt;/b&gt;</div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">The three major types of glial cells in the CNS are astrocytes, oligodendrocytes, and microglial cells (Fig. 11-9, Table 11-3). As discussed in Chapter 10, the peripheral nervous system (PNS) contains other, distinctive types of glial cells, including satellite cells, Schwann cells, and enteric glia. Glial cells represent about half the volume of the brain and are more numerous than neurons. Unlike neurons, which have little capacity to replace themselves when lost, neuroglial (or simply glial) cells can proliferate throughout life. An injury to the nervous system is the usual stimulus for proliferation.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">CNS 中的三种主要神经胶质细胞类型是星形胶质细胞、少突胶质细胞和小胶质细胞（图 11-9、表 11-3）。如第 10 章所述，周围神经系统 （PNS） 包含其他独特类型的神经胶质细胞，包括卫星细胞、雪旺细胞和肠道神经胶质细胞。神经胶质细胞约占大脑体积的一半，比神经元多。与神经元不同，神经元在丢失时几乎没有自我替换的能力，神经胶质细胞（或简称神经胶质细胞）可以在一生中增殖。神经系统损伤是增殖的常见刺激因素。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Historically, glial cells were viewed as a type of CNS connective tissue whose main function was to provide support for the true functional cells of the brain, the neurons. This firmly entrenched concept remained virtually unquestioned for the better part of a century after the early description of these cells by Virchow in 1858. Knowledge about glial cells has accumulated slowly because these cells have proved far more difficult to study than neurons. Because glial cells do not exhibit easily recorded action potentials or synaptic potentials, these cells were sometimes referred to as silent cells. However, glial cells are now recognized as intimate partners with neurons in virtually every function of the brain.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">从历史上看，神经胶质细胞被视为一种 CNS 结缔组织，其主要功能是为大脑的真正功能细胞神经元提供支持。在 1858 年 Virchow 对这些细胞进行早期描述后的大部分时间里，这个根深蒂固的概念几乎没有受到质疑。关于神经胶质细胞的知识积累得很慢，因为事实证明这些细胞比神经元更难研究。由于神经胶质细胞不表现出容易记录的动作电位或突触电位，因此这些细胞有时被称为沉默细胞。然而，神经胶质细胞现在被认为与大脑几乎所有功能的神经元紧密结合。</ins></div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td></tr> </table>

Comcat http://wiki.jackslab.org/index.php?title=Ch11_The_Neuronal_Microenvironment&diff=17998&oldid=prev 2024-12-11T09:48:55Z

<p>‎<span dir="auto"><span class="autocomment">毛细血管内皮细胞的运输有助于血脑屏障</span></span></p> <table class='diff diff-contentalign-left'> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr valign='top'> <td colspan='2' style="background-color: white; color:black;">←上一版本</td> <td colspan='2' style="background-color: white; color:black;">2024年12月11日 (三) 09:48的版本</td> </tr><tr><td colspan="2" class="diff-lineno">第258行：</td> <td colspan="2" class="diff-lineno">第258行：</td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 毛细血管内皮细胞的运输有助于血脑屏障 ===</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 毛细血管内皮细胞的运输有助于血脑屏障 ===</div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;Transport by capillary endothelial cells contributes to the blood-brain barrier&lt;/b&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;Transport by capillary endothelial cells contributes to the blood-brain barrier&lt;/b&gt;</div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Two classes of substances can pass readily between blood and brain. The first consists of the small, highly lipid-soluble molecules discussed in the preceding section. The second group consists of water-soluble compounds—either critical nutrients entering or metabolites exiting the brain—that traverse the BBB by specific transporters. Examples include glucose, several amino acids and neurotransmitters, nucleic acid precursors, and several organic acids. Two major transporter groups provide these functions: the SLC superfamily (see pp. 111–114) and ABC transporters (see pp. 119–120). N11-3 As is the case for other epithelial cells, capillary endothelial cells selectively express these and other membrane proteins on either the luminal or basal surface.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">两类物质可以很容易地在血液和大脑之间传递。第一个由上一节中讨论的高脂溶性小分子组成。第二组由水溶性化合物组成——进入大脑的关键营养物质或离开大脑的代谢物——它们通过特定的转运蛋白穿过 BBB。例子包括葡萄糖、几种氨基酸和神经递质、核酸前体和几种有机酸。两个主要的转运蛋白组提供这些功能：SLC 超家族（参见第 111-114 页）和 ABC 转运蛋白（参见第 119-120 页）。N11-3 与其他上皮细胞一样，毛细血管内皮细胞选择性地在管腔或基底表面表达这些和其他膜蛋白。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Although the choroid plexuses secrete most of the CSF, brain endothelial cells produce some interstitial fluid with a composition similar to that of CSF. Transporters such as those shown in Figure 11-8C are responsible for this CSFlike secretion as well as for the local control of [K+] and pH in the BECF.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">虽然脉络丛分泌大部分脑脊液，但脑内皮细胞会产生一些成分类似于脑脊液的间质液。如图 11-8C 所示的转运蛋白负责这种 CSF 样分泌以及 BECF 中 [K+] 和 pH 值的局部控制。</ins></div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td></tr> </table>

Comcat http://wiki.jackslab.org/index.php?title=Ch11_The_Neuronal_Microenvironment&diff=17997&oldid=prev 2024-12-11T09:47:37Z

<p>‎<span dir="auto"><span class="autocomment">不带电和脂溶性分子更容易通过血脑屏障</span></span></p> <table class='diff diff-contentalign-left'> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr valign='top'> <td colspan='2' style="background-color: white; color:black;">←上一版本</td> <td colspan='2' style="background-color: white; color:black;">2024年12月11日 (三) 09:47的版本</td> </tr><tr><td colspan="2" class="diff-lineno">第244行：</td> <td colspan="2" class="diff-lineno">第244行：</td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 不带电和脂溶性分子更容易通过血脑屏障 ===</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 不带电和脂溶性分子更容易通过血脑屏障 ===</div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;Uncharged and lipid-soluble molecules more readily pass through the blood-brain barrier&lt;/b&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;Uncharged and lipid-soluble molecules more readily pass through the blood-brain barrier&lt;/b&gt;</div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">The capacity of the brain capillaries to exclude large molecules is strongly related to the molecular mass of the molecule and its hydrated diameter (Table 11-2). With a mass of 61 kDa, prealbumin is 14 times as concentrated in blood as in CSF (essentially equivalent to BECF for purposes of this comparison), whereas fibrinogen, which has a molecular mass of 340 kDa, is ~5000 times more concentrated in blood than in CSF. Diffusion of a solute is also generally limited by ionization at physiological pH, by low lipid solubility, and by binding to plasma proteins. For example, gases such as CO2 and O2 and drugs such as ethanol, caffeine, nicotine, heroin, and methadone readily cross the BBB. However, ions such as K+ or Mg2+ and protein-bound metabolites such as bilirubin have restricted access to the brain. Finally, the BBB is permeable to water mainly because of the presence of AQP4 in the astrocytic endfeet (see Fig. 11-8A). Thus, water moves across the BBB in response to changes in plasma osmolality. When dehydration raises the osmolality of blood plasma (see Box 11-3), the increased osmolality of the CSF and BECF can affect the behavior of brain cells.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">脑毛细血管排除大分子的能力与分子的分子量及其水合直径密切相关（表 11-2）。质量为 61 kDa，前白蛋白在血液中的浓度是 CSF 中的14倍（基本上相当于本比较中的BECF），而纤维蛋白原的分子量为 340 kDa，在血液中的浓度是 CSF 中的 ~5000 倍。溶质的扩散通常也受到生理 pH 值下电离、低脂质溶解度以及与血浆蛋白结合的限制。例如，CO2 和 O2 等气体以及乙醇、咖啡因、尼古丁、海洛因和美沙酮等药物很容易穿过 BBB。然而，离子（如 K+ 或 Mg2+）和蛋白质结合的代谢物（如胆红素）对大脑的访问受到限制。最后，BBB 对水具有渗透性，主要是因为星形胶质细胞终足中存在 AQP4（见图 11-8A）。因此，水响应血浆渗透压的变化而穿过 BBB。当脱水提高血浆的渗透压时（见框 11-3），CSF 和 BECF 的渗透压增加会影响脑细胞的行为。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Cerebral capillaries also express enzymes that can affect the movement of substances from blood to brain and vice versa. Peptidases, acid hydrolases, monoamine oxidase, and other enzymes are present in CNS endothelial cells and can degrade a range of biologically active molecules, including enkephalins, substance P, proteins, and norepinephrine. Orally administered dopamine is not an effective treatment of Parkinson disease (see p. 313), a condition in which CNS dopamine is depleted, because dopamine is rapidly broken down by monoamine oxidase in the capillaries. Fortunately, the dopamine precursor compound L-DOPA is effective for this condition. Neutral amino-acid transporters in capillary endothelial cells move L-DOPA to the BECF, where presynaptic terminals take up the L-DOPA and convert it to dopamine in a reaction that is catalyzed by DOPA decarboxylase.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">脑毛细血管还表达酶，这些酶可以影响物质从血液到大脑的运动，反之亦然。肽酶、酸性水解酶、单胺氧化酶和其他酶存在于 CNS 内皮细胞中，可以降解一系列生物活性分子，包括脑啡肽、P 物质、蛋白质和去甲肾上腺素。口服多巴胺不是帕金森病的有效治疗方法（见第 313 页），帕金森病是一种 CNS 多巴胺耗尽的情况，因为多巴胺在毛细血管中被单胺氧化酶迅速分解。幸运的是，多巴胺前体化合物 L-DOPA 对这种情况有效。毛细血管内皮细胞中的中性氨基酸转运蛋白将 L-DOPA 移动到 BECF，在那里突触前末端吸收 L-DOPA 并在 DOPA 脱羧酶催化的反应中将其转化为多巴胺。</ins></div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td></tr> </table>

Comcat http://wiki.jackslab.org/index.php?title=Ch11_The_Neuronal_Microenvironment&diff=17996&oldid=prev 2024-12-11T09:45:45Z

<p>‎<span dir="auto"><span class="autocomment">连续的紧密连接连接大脑毛细血管内皮细胞</span></span></p> <table class='diff diff-contentalign-left'> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr valign='top'> <td colspan='2' style="background-color: white; color:black;">←上一版本</td> <td colspan='2' style="background-color: white; color:black;">2024年12月11日 (三) 09:45的版本</td> </tr><tr><td colspan="2" class="diff-lineno">第221行：</td> <td colspan="2" class="diff-lineno">第221行：</td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 连续的紧密连接连接大脑毛细血管内皮细胞 ===</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 连续的紧密连接连接大脑毛细血管内皮细胞 ===</div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;Continuous tight junctions link brain capillary endothelial cells&lt;/b&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;Continuous tight junctions link brain capillary endothelial cells&lt;/b&gt;</div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">The BBB should be thought of as a physical barrier to diffusion from blood to BECF and as a selective set of regulatory transport mechanisms that determine how certain organic solutes move between the blood and brain. Thus, the BBB contributes to stabilization and protection of the neuronal microenvironment by facilitating the entry of needed substances, removing waste metabolites, and excluding toxic or disruptive substances.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">BBB 应被视为从血液扩散到 BECF 的物理屏障，以及一组选择性的调节运输机制，用于确定某些有机溶质如何在血液和大脑之间移动。因此，BBB 通过促进所需物质的进入、去除废物代谢物以及排除有毒或破坏性物质，有助于稳定和保护神经元微环境。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">The structure of brain capillaries differs from that of capillaries in other organs (Fig. 11-8A). Capillaries in other organs generally have small, simple openings—or clefts— between their endothelial cells. In some of these other organs, windows, or fenestrae, provide a pathway that bypasses the cytoplasm of capillary endothelial cells. Thus, in most capillaries outside the CNS, solutes can easily diffuse through the clefts and fenestrae. The physical barrier to solute diffusion in brain capillaries (see Fig. 11-8B) is provided by the capillary endothelial cells, which are fused to each other by continuous tight junctions (or zonula occludens; see pp. 43–44). The tight junctions prevent watersoluble ions and molecules from passing from the blood into the brain through the paracellular route. Not surprisingly, the electrical resistance of the cerebral capillaries is 100 to 200 times higher than that of most other systemic capillaries.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">脑毛细血管的结构与其他器官的毛细血管不同（图 11-8A）。其他器官的毛细血管通常在其内皮细胞之间有小而简单的开口或裂缝。在一些其他器官中，窗户或门口提供了绕过毛细血管内皮细胞细胞质的通路。因此，在 CNS 外的大多数毛细血管中，溶质很容易通过裂隙和孔隙扩散。溶质在脑毛细血管中扩散的物理屏障（见图 11-8B）由毛细血管内皮细胞提供，它们通过连续的紧密连接（或小带闭塞;见第 43-44 页）相互融合。紧密连接可防止水溶性离子和分子通过细胞旁途径从血液进入大脑。毫不奇怪，大脑毛细血管的电阻比大多数其他全身毛细血管的电阻高 100 到 200 倍。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Elsewhere in the systemic circulation, molecules may traverse the endothelial cell by the process of transcytosis (see p. 467). In cerebral capillaries, transcytosis is uncommon, and brain endothelial cells have fewer endocytic vesicles than do systemic capillaries. However, brain endothelial cells have many more mitochondria than systemic endothelial cells do, which may reflect the high metabolic demands imposed on brain endothelial cells by active transport.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">在体循环的其他地方，分子可能通过转胞吞作用过程穿过内皮细胞（见第 467 页）。在脑毛细血管中，转胞吞作用不常见，脑内皮细胞的内吞囊泡比全身毛细血管少。然而，脑内皮细胞的线粒体比全身内皮细胞多得多，这可能反映了主动运输对脑内皮细胞的高代谢需求。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Other interesting features of brain capillaries are the thick basement membrane that underlies the endothelial cells, the presence of occasional pericytes within the basement membrane sheath, and the astrocytic endfeet (or processes) that provide a nearly continuous covering of the capillaries and other blood vessels. Astrocytes may play a crucial role in forming tight junctions between endothelial cells; experiments have shown that these glial cells can induce the formation of tight junctions between endothelial cells derived from capillaries outside the CNS. The close apposition of the astrocyte endfoot to the capillary also could facilitate transport of substances between these cells and blood.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">脑毛细血管的其他有趣特征是内皮细胞下方的厚基底膜、基底膜鞘内偶尔存在的周细胞，以及提供几乎连续覆盖毛细血管和其他血管的星形胶质细胞终足（或过程）。星形胶质细胞可能在内皮细胞之间形成紧密连接方面起关键作用;实验表明，这些神经胶质细胞可以诱导来源于 CNS 外毛细血管的内皮细胞之间形成紧密连接。星形胶质细胞终足与毛细血管的紧密结合也可以促进这些细胞和血液之间的物质运输。</ins></div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td></tr> </table>

Comcat http://wiki.jackslab.org/index.php?title=Ch11_The_Neuronal_Microenvironment&diff=17995&oldid=prev 2024-12-11T09:42:46Z

<p>‎<span dir="auto"><span class="autocomment">血脑屏障阻止一些血液成分进入大脑细胞外间隙</span></span></p> <table class='diff diff-contentalign-left'> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr valign='top'> <td colspan='2' style="background-color: white; color:black;">←上一版本</td> <td colspan='2' style="background-color: white; color:black;">2024年12月11日 (三) 09:42的版本</td> </tr><tr><td colspan="2" class="diff-lineno">第197行：</td> <td colspan="2" class="diff-lineno">第197行：</td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 血脑屏障阻止一些血液成分进入大脑细胞外间隙 ===</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>=== 血脑屏障阻止一些血液成分进入大脑细胞外间隙 ===</div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;The blood-brain barrier prevents some blood constituents from entering the brain extracellular space&lt;/b&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;b style=color:#0ae&gt;The blood-brain barrier prevents some blood constituents from entering the brain extracellular space&lt;/b&gt;</div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">The unique protective mechanism now called the BBB was first demonstrated by Ehrlich in 1885. He injected aniline dyes intravenously and discovered that the soft tissues of the body, except for the brain, were uniformly stained. Aniline dyes, such as trypan blue, extensively bind to serum albumin, and the dye-albumin complex passes across capillaries in most areas of the body, but not the brain. This ability to exclude certain substances from crossing CNS blood vessels into the brain tissue is due to the blood-brain barrier. We now recognize that a BBB is present in all vertebrates and many invertebrates as well.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">现在称为 BBB 的独特保护机制由 Ehrlich 于 1885 年首次演示。他静脉注射苯胺染料，发现身体的软组织，除了大脑，都是均匀染色的。苯胺染料（如台盼蓝）与血清白蛋白广泛结合，染料-白蛋白复合物穿过身体大多数部位的毛细血管，但不穿过大脑。这种排除某些物质穿过 CNS 血管进入脑组织的能力是由于血脑屏障。我们现在认识到 BBB 存在于所有脊椎动物和许多无脊椎动物中。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">The need for a BBB can be understood by considering that blood is not a suitable environment for neurons. Blood is a complex medium that contains a large variety of solutes, some of which can vary greatly in concentration, depending on factors such as diet, metabolism, illness, and age. For example, the concentration of many amino acids increases significantly after a protein-rich meal. Some of these amino acids act as neurotransmitters within the brain, and if these molecules could move freely from the blood into the neuronal microenvironment, they would nonselectively activate receptors and disturb normal neurotransmission. Similarly, strenuous exercise can increase plasma concentrations of K+ and H+ substantially. If these ionic changes were communicated directly to the microenvironment of neurons, they could disrupt ongoing neural activity. Running a foot race might temporarily lower your IQ. Increases in [K+]o would depolarize neurons and thus increase their likelihood of firing and releasing transmitter. H+ can nonspecifically modulate neuronal excitability and influence the action of certain neurotransmitters. A broad range of blood constituents—including hormones, other ions, and inflammatory mediators such as cytokines—can influence the behavior of neurons or glial cells, which can express receptors for these molecules. For the brain to function efficiently, it must be spared such influences.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">通过考虑血液不适合神经元的环境，可以理解对 BBB 的需求。血液是一种复杂的介质，含有多种溶质，其中一些溶质的浓度会有很大差异，具体取决于饮食、新陈代谢、疾病和年龄等因素。例如，在富含蛋白质的膳食后，许多氨基酸的浓度会显着增加。其中一些氨基酸在大脑中充当神经递质，如果这些分子可以从血液中自由移动到神经元微环境中，它们就会非选择性地激活受体并干扰正常的神经传递。同样，剧烈运动可以显着增加血浆中 K+ 和 H+ 的浓度。如果这些离子变化直接传达给神经元的微环境，它们可能会破坏正在进行的神经活动。跑步可能会暂时降低您的智商。[K+]o 的增加会使神经元去极化，从而增加它们发射和释放递质的可能性。H+ 可以非特异性调节神经元兴奋性并影响某些神经递质的作用。广泛的血液成分（包括激素、其他离子和炎症介质，如细胞因子）可以影响神经元或神经胶质细胞的行为，而神经元或神经胶质细胞可以表达这些分子的受体。为了让大脑有效运作，它必须免受这种影响。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">The choroid plexus and several restricted areas of the brain lack a BBB; that is, they are supplied by leaky capillaries. Intra-arterially injected dyes can pass into the BECS at these sites through gaps between endothelial cells. The BECF in the vicinity of these leaky capillaries is more similar to blood plasma than to normal BECF. The small brain areas that lack a BBB are called the circumventricular organs because they surround the ventricular system; these areas include the area postrema, posterior pituitary, median eminence, organum vasculosum laminae terminalis, subfornical organ, subcommissural organ, and pineal gland (Fig. 11-7). The ependymal cells that overlie the leaky capillaries in some of these regions (e.g., the choroid plexus) are linked together by tight junctions that form a barrier between the local BECF and the CSF, which must be insulated from the variability of blood composition. Whereas dyes with molecular weights up to 5000 can normally pass from CSF across the ependymal cell layer into the BECF, they do not pass across the specialized ependymal layer at the median eminence, area postrema, and infundibular recess. At these points, the localized BECF-CSF barrier is similar to the one in the choroid plexus. These specialized ependymal cells often have long processes that extend to capillaries within the portal circulation of the pituitary. Although the function of these cells is not known, it has been suggested that they may form a special route for neurohumoral signaling; molecules secreted by hypothalamic cells into the third ventricle could be taken up by these cells and transmitted to the general circulation or to cells in the pituitary.</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">脉络丛和大脑的几个受限区域缺乏 BBB;也就是说，它们是由渗漏的毛细血管供应的。动脉内注射的染料可以通过内皮细胞之间的间隙进入这些部位的 BECS。这些渗漏的毛细血管附近的 BECF 比正常 BECF 更类似于血浆。缺乏 BBB 的小脑区称为脑室周围器官，因为它们围绕着心室系统;这些区域包括极后区、垂体后叶、正中隆起、器官血管终板、穹窿下器官、连合下器官和松果体（图 11-7）。在其中一些区域（例如脉络丛）中覆盖渗漏毛细血管的室管膜细胞通过紧密连接连接在一起，这些连接在局部 BECF 和 CSF 之间形成屏障，CSF 必须与血液成分的变化隔离。虽然分子量高达 5000 的染料通常可以从 CSF 穿过室管膜细胞层进入 BECF，但它们不会穿过正中隆起、极后区和漏斗部隐窝处的特化室管膜层。在这些点上，定位的 BECF-CSF 屏障类似于脉络丛中的屏障。这些特化的室管膜细胞通常具有延伸到垂体门静脉循环内的毛细血管的长过程。虽然这些细胞的功能尚不清楚，但有人认为它们可能形成神经体液信号传导的特殊途径;下丘脑细胞分泌到第三脑室的分子可以被这些细胞吸收并传递到全身循环或垂体中的细胞。</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">Neurons within the circumventricular organs are directly exposed to blood solutes and macromolecules; this arrangement is believed to be part of a neuroendocrine control system for maintaining such parameters as osmolality (see p. 844) and appropriate hormone levels, among other things. Humoral signals are integrated by connections of circumventricular organ neurons to endocrine, autonomic, and behavioral centers within the CNS. In the median eminence, neurons discharge “releasing hormones,” which diffuse into leaky capillaries for carriage through the pituitary portal system to the anterior pituitary (see p. 978). The lack of a BBB in the posterior pituitary is necessary to allow hormones that are released there to enter the general circulation (see p. 979). In the organum vasculosum laminae terminalis, leakiness is important in the action of cytokines from the periphery, which act as signals to temperature control centers that are involved in fever (see p. 1202).</ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;"></ins></div></td></tr> <tr><td colspan="2">&#160;</td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><ins style="color: red; font-weight: bold; text-decoration: none;">脑室周围器官内的神经元直接暴露于血液溶质和大分子;这种安排被认为是神经内分泌控制系统的一部分，用于维持渗透压（见第 844 页）和适当的激素水平等参数。体液信号通过脑室周围器官神经元与 CNS 内的内分泌、自主神经和行为中心的连接进行整合。在正中隆起处，神经元释放“释放激素”，这些激素扩散到渗漏的毛细血管中，通过垂体门系统到达垂体前叶（见第 978 页）。垂体后叶缺乏 BBB 是允许在那里释放的激素进入全身循环所必需的（见第 979 页）。在器官血管终梢层中，渗漏在来自外周的细胞因子的作用中很重要，这些细胞因子充当与发烧有关的温度控制中心的信号（见第 1202 页）。</ins></div></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td><td class='diff-marker'>&#160;</td><td style="background: #eee; color:black; font-size: smaller;"><div>&lt;br&gt;</div></td></tr> </table>

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